Yongsik Jung

The Korean Hereditary Breast Cancer (KOHBRA) Study: Protocols and Interim Report

AIMS The primary aims of the Korean Hereditary Breast Cancer (KOHBRA) study are to estimate the prevalence of BRCA1/2 mutations and ovarian cancer among a high-risk group of patients with hereditary breast cancer and their families. MATERIALS AND METHODS The KOHBRA study is a prospective multicentre cohort identifying cases and their families. Between May 2007 and May 2010, the KOHBRA study enrolled up to 2000 subjects. All participants received genetic counselling and BRCA genetic testing; the clinical information and blood samples for blood banking were collected. An interim analysis of the prevalence of BRCA1/2 mutations and ovarian cancer in Korean subjects was determined from the initial 975 patients who presented to 33 centres. RESULTS By April 2009, a total of 167 mutation carriers among 853 probands were identified. The prevalence of the BRCA mutation was as follows: 24.8% (106/428) for breast cancer patients with a family history of breast/ovarian cancers; 11.3% (24/212) for patients with early-onset (<35 years) breast cancer without a family history; 22.1% (15/68) for patients with bilateral breast cancer; male breast cancer in 8.3% (1/12); and 33.4% (1/3) for patients with breast and ovarian cancer. CONCLUSIONS The results of this study suggest that the prevalence of BRCA mutations in Korean subjects is similar to the prevalence reported among Western cohorts. However, weak family history and non-familial early-onset of breast cancer were significant factors associated with carrying the BRCA mutation in Korean breast cancer patients. Completion of the KOHBRA study is needed to confirm these findings.

Diazoxide acts more as a PKC‐ɛ activator, and indirectly activates the mitochondrial KATP channel conferring cardioprotection against hypoxic injury

Diazoxide, a well‐known opener of the mitochondrial ATP‐sensitive potassium (mitoKATP) channel, has been demonstrated to exert cardioprotective effect against ischemic injury through the mitoKATP channel and protein kinase C (PKC). We aimed to clarify the role of PKC isoforms and the relationship between the PKC isoforms and the mitoKATP channel in diazoxide‐induced cardioprotection.

Hair iron and other minerals' level in breast cancer patients.

Little is known about hair minerals in cancer patients, and serum iron level has been shown to be elevated in breast cancer patients. Therefore, the aim of this study was to evaluate hair iron and hair minerals’ level related to hair iron in breast cancer patients compared to controls. We compared hair mineral analysis data of 40 breast cancer subjects with age and body mass index-matched normal control data (n = 144) by cross-sectional analysis. All breast cancer patients were newly diagnosed at one Breast Cancer Center in Ajou University and had their hair cut before anti-cancer chemotherapy, and the normal controls (without breast cancer) also had their hair cut for various reasons in out-patient clinics of the Department of Family Practice and Community Health. Breast cancer patients had low calcium, magnesium, iron, copper, manganese, and zinc, whereas they had high arsenic, sodium, and potassium compared with the normal control. The hair iron level was positively correlated with hair calcium (r = 0.761, P < 0.001), magnesium (r = 0.643, P < 0.001), and manganese (r = 0.550, P < 0.001) and negatively correlated with arsenic (r = −0.537, P < 0.001). The hair iron level was significantly associated with the hair calcium (β = 0.778, P < 0.001) and manganese (β = 0.240, P < 0.001) by using multiple linear regression analysis. We observed different hair mineral patterns in breast cancer patients compared to normal controls. Especially, hair iron level was significantly reduced and associated with hair calcium and manganese levels.

Chemotherapy-related amenorrhea in premenopausal women with breast cancer.

Objective: To report the incidence of chemotherapy-related amenorrhea (CRA) from chemotherapy with/without adjuvant endocrine therapy in premenopausal women with breast cancer and to analyze the related factors. Design: From January 2000 to August 2006, 326 premenopausal women (≤50 y old) who completed chemotherapy were available for analysis. The CRA definitional criterion in this study was no menstruation for 6 months in a woman who was premenopausal at diagnosis. As risk factors for CRA, womans age, the type of chemotherapy regimen, adjuvant endocrine therapy use, and body mass index were evaluated. Results: The median age was 42 years (range, 22-50 y). The median follow-up period was 37 months (range, 12-80 mo). Women were divided into two groups by age at diagnosis: 128 women in group 1 (less than 40 years old) and 198 women in group 2 (age ≥40 y). CRA occurred in a total of 223 (68%) women: 43% in group 1 and 85% in group 2 (P < 0.001). Despite CRA, 14% resumed menstruation: 24% in group 1 and 11% in group 2. Another 40 (12%) women had less than 6 months of menstruation interruption. Permanent CRA was related with age at diagnosis and use of adjuvant endocrine therapy (P < 0.05). In this study, there were four pregnancies, two of which resulted in therapeutic abortion due to ongoing chemotherapy. Conclusions: This study confirmed that the rate of CRA depends on age at diagnosis and the use of adjuvant endocrine therapy. It is essential to inform young women of reproductive age of the possibility of amenorrhea or resumption of menstruation and contraceptive options.

Evaluation of lymph node status after neoadjuvant chemotherapy in breast cancer patients: comparison of diagnostic performance of ultrasound, MRI and 18F-FDG PET/CT

Objective: To evaluate the diagnostic performance of ultrasound, MRI and fluorine-18 fludeoxyglucose positron emission tomography (18F-FDG PET)/CT for the diagnosis of metastatic axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC) and to find out histopathological factors affecting the diagnostic performance of these imaging modalities. Methods: From January 2012 to November 2014, 191 consecutive patients with breast cancer who underwent NAC before surgery were retrospectively reviewed. We included 139 patients with ALN metastasis that was confirmed on fine needle aspiration or core needle biopsy at initial diagnosis. Results: After NAC, 39 (28%) patients showed negative conversion of ALN on surgical specimens of sentinel lymph node (LN) or ALN. The sensitivity of ultrasound, MRI and PET/CT was 50% (48/96), 72% (70/97) and 22% (16/73), respectively. The specificity of ultrasound, MRI and PET/CT was 77% (30/39), 54% (21/39) and 85% (22/26), respectively. The Az value of combination of ultrasound and PET/CT was the highest (0.634) followed by ultrasound (0.626) and combination of ultrasound, MRI and PET/CT (0.617). The size of tumour deposit in LN and oestrogen receptor was significantly associated with the diagnostic performance of ultrasound (p < 0.001 and p = 0.009, respectively) and MRI (p = 0.045 and p = 0.036, respectively). The percentage diameter decrease, size of tumour deposit in LN, progesterone receptor, HER2 and histological grade were significantly associated with the diagnostic performance of PET/CT (p = 0.023, p = 0.002, p = 0.036, p = 0.044 and p = 0.008, respectively). On multivariate logistic regression analysis, size of tumour deposit within LN was identified as being independently associated with diagnostic performance of ultrasound [odds ratio, 13.07; 95% confidence interval (CI), 2.95–57.96] and PET/CT (odds ratio, 6.47; 95% CI, 1.407–29.737). Conclusion: Combination of three imaging modalities showed the highest sensitivity, and PET/CT showed the highest specificity for the evaluation of ALN metastasis after NAC. Ultrasound alone or combination of ultrasound and PET/CT showed the highest positive-predictive value. The size of tumour deposit within ALN was significantly associated with diagnostic performance of ultrasound and PET/CT. Advances in knowledge: This study is about the diagnostic performance of ultrasound, MRI, PET/CT and combination of each imaging modality for the evaluation of metastatic ALN after NAC. Of many histopathological factors, only the size of tumour deposit within ALN was an independent factor associated with the diagnostic performance of ultrasound and PET/CT.

Effect of DA-9701, a novel prokinetic agent, on stress-induced delayed gastric emptying and hormonal changes in rats

Background  DA‐9701 is a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber. This study aimed to evaluate the effect of DA‐9701 on stress‐induced delay in gastric emptying and changes in plasma adrenocorticotropic hormone and ghrelin levels in rats.

[Prevalence and characteristics of chemotherapy-related cognitive impairment in patients with breast cancer].

PURPOSE Evidence suggests that some patients with breast cancer experience cognitive difficulties following chemotherapy. This longitudinal study was done to examine the prevalence of cognitive impairment and trajectory of cognitive function over time in women with breast cancer, who received adjuvant chemotherapy. METHODS Participants were 137 patients with breast cancer. They completed neuropsychological tests and the Functional Assessment of Cancer Therapy-Cognitive Function before adjuvant therapy (pretest), toward the end of adjuvant therapy (posttest), and 6 months after the completion of adjuvant therapy (follow-up test). Of the patients, 91 were treated with adjuvant chemotherapy and 46 patients who did not receive chemotherapy made up the comparison group. A reliable-change index and repeated-measure ANOVA were used for statistical analyses. RESULTS At the posttest point, over 30% of patients showed complex cognitive impairment and reported greater difficulty in subjective cognitive function. At the follow-up test point, 22.0% of patients exhibited complex cognitive impairment and 30.8% of patients complained of subjective cognitive impairment. Repeated-measure ANOVA showed significant decreases after receiving chemotherapy followed by small improvements 6 months after the completion of chemotherapy in cognitive domains of change for attention and concentration, memory, executive function, and subjective cognitive function. CONCLUSION These results suggest that chemotherapy in patients with breast cancer may be associated with objective and subjective cognitive impairments. Further studies are needed to explore the potential risk factors and predictor of chemotherapy-related cognitive changes. Also nursing interventions for prevention and intervention of cognitive impairments should be developed and tested.

Dietary intake and breast cancer among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study

BACKGROUND Soy intake is associated with a lower risk of breast cancer. However, it is unclear whether the same reduction in risk associated with high soy intake is also applicable to familial or genetic breast cancer. OBJECTIVE The aim of this study was to assess the dietary factors among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study (KOHBRA). DESIGN The KOHBRA Study is an ongoing project composed of affected breast cancer patients and familial members of breast cancer cases with BRCA mutations. To assess the association between dietary diversity and breast cancer risk, an HR was estimated by comparing affected subjects with their familial nonaffected members. To assess the interaction between the combination of BRCA mutation and diet diversity, the case-only OR (COR) was estimated by comparing BRCA mutation carriers and noncarriers only in affected subjects. RESULTS Soy product intake was associated with a lower risk of breast cancer in carriers (HR: 0.39; 95% CI: 0.19, 0.79 for the highest quartile). The highest quartile of meat intake was associated with a higher risk of breast cancer regardless of BRCA mutation in carriers (HR: 1.97; 95% CI: 1.13, 3.44) and noncarriers (95% CI: 1.41; 1.12, 1.78). The associations of meat intake and soybean intake for breast cancer were more prominent in BRCA2 mutation carriers. In the analysis with only cases, the highest quartile of soy intake, but not meat intake, was associated with BRCA-related breast cancer (COR: 0.57; 95% CI: 0.36, 0.91). CONCLUSION Our study suggests that soy product consumption is associated with lower breast cancer risk and it had an interaction with BRCA mutation.

Sentinel Lymph Node Biopsy Alone after Neoadjuvant Chemotherapy in Patients with Initial Cytology-Proven Axillary Node Metastasis

Purpose Neoadjuvant chemotherapy (NAC) has been recently used to downstage breast cancer. However, in patients with initial axillary lymph node (ALN) metastasis, ALN dissection regardless of the NAC response remains the standard treatment. The purpose of this study was to identify the feasibility and accuracy of sentinel lymph node biopsy (SLNB) after NAC in patients with ALN metastasis at diagnosis. Methods From January 2007 to August 2013, data of patients who were diagnosed with invasive breast cancer and ALN metastasis and treated with NAC followed by definitive surgery in two centers were collected retrospectively. A total of 386 patients were enrolled and classified into five groups according to surgical procedure for the ALNs and pathologic results. Results At SLNB after NAC, sentinel lymph nodes (SLNs) that stained blue or were hot, including suspicious nodes, were identified; the SLN identification and false-negative rates was 96% and 10%, respectively. There was no difference in the overall survival among the groups. For patients who revealed a pathologic complete node response, there was a significant difference in the disease-free survival rate between the SLNB only and complete ALN dissection groups (p=0.031). However, the rate of axillary recurrence demonstrated no significant differences among the groups (p>0.050). Conclusion SLNB after NAC in breast cancer patients with initial ALN metastasis may help identify downstaging to negative nodal status and thereby reduce the surgical morbidity by avoiding standard ALN dissection.

Cyclooxygenase-2 expression in human thyroid disease

Objectives: Cyclooxygenase (COX)-2, which is the inducible form of the COX enzyme for prostaglandin synthesis and a key mediator of epithelial cell growth, has been shown to be up-regulated in gastrointestinal cancers. Additionally, regular intake of other non-steroidal anti-inflammatory drugs (NSAID) is known to decrease the incidence of these cancers. Therefore, the goals of the present study were to determine the possible involvement of COX-2 in human thyroid diseases. Methods: We used immunohistochemical staining and Western blot analysis to characterize the expression of COX-2 proteins in thyroid tissues from 64 patients with thyroiditis, benign tumors, and malignant tumors with or without metastasis. Immunoreactivity scores were calculated by multiplication of the determined grades. Results: COX-2 proteins were not expressed in normal thyroid tissues. However, each type of tumor tissue showed intense bands of COX-2 protein expression in Western blot analyses, and the immunoreactivity scores were 7.67±1.17 (SD) for thyroiditis, 7.87±0.9 for benign tumors, 7.53±1.53 for follicular cancer, 7.63±1.11 for papillary cancer without metastasis, and 7.17±1.55 for papillary cancer with metastasis. No significant differences were found in the levels of COX-2 expression between different tumor tissue types. Conclusion: No significant correlations were observed between clinical and/or pathological characteristics of thyroid tumors and the intensity of COX-2 protein expression. In addition, we found no difference in COX-2 protein expression between thyroiditis and thyroid tumors. Thus, up-regulation of COX-2 protein synthesis in human thyroid diseases does not appear to be of clinical significance.